Osteoporosis (OP) is a generalized skeletal system disease characterized by reduced bone mass and degenerated microstructure of bone tissue, leading to decreased bone strength, increased bone fragility, and increased risk of fractures. Bone remodeling is a process of self-renewal of bone tissue, where osteoclasts constantly absorb the old bone, and osteoblasts constantly form a new bone to supplement the bone parts which have been absorbed. The osteoclasts play an important role in the bone remodeling process after the body's bones grow to maturity. Enhanced activity or increased amount of osteoclasts can lead to increased bone resorption and bone remodeling imbalance, resulting in the occurrence of many skeletal system diseases, such as osteoporosis. The most common complication of osteoporosis is fracture, which normally occurs at the hip, vertebral body, and distal radius. After women go into menopause, bone mass loss is significant, and if there is no appropriate prevention and treatment, osteoporosis will inevitably lead to fractures at radius, vertebral column and hip, etc. With the population aging and the extension of average human lifespan, the worldwide incidence of osteoporotic fracture increases at an average rate of greater than 1% per year. Therefore, one of the main tasks at present is to study more effective and simple means assisting in treating osteoporotic fracture so as to satisfy the needs of different groups of people.
Bisphosphonate (BP) drugs are a new class of drugs developed over the past 30 years, and mainly used for the treatment and prevention of bone metastases of malignant tumor and bone metabolic diseases, such as osteoporosis and Paget's disease. BPs are divided into three generations according to the strength of the effect of the drug or the time to market of the drug. The first generation is BP free of nitrogen, which is a product available mainly during the 1970s and 1980s. The second generation of BP has a significantly better resistance to bone resorption than the first generation product and is primarily featured by containing amino group in the structure thereof. The third generation of BP is the latest generation of drugs, which is available to the market at the end of the last century and the beginning of the present century, has an even stronger resistance to bone resorption, and is more convenient for clinical application, and ibandronate sodium is a typical product thereof.
Ibandronate sodium, as a potent osteoclast inhibitor, is specifically bindable to hydroxyapatite in bones, which can not only inhibit the activity of osteoclasts but also induce apoptosis of osteoclasts, which are the direct effects of ibandronate sodium. Moreover, ibandronate sodium can also act on osteoblasts, and release one or more osteoclast renewal inhibitors by the latter, thereby shortening the lifespan of osteoclasts and reducing the number of osteoclasts. Therefore, ibandronate sodium can treat and prevent osteoporosis when applied to the whole body, and can assist in promoting fracture healing, particularly fractures caused by osteoporosis, when applied locally to the fracture sites. However, treatment with ibandronate sodium-related drugs has some side effects. A few patients may show an increase in body temperature, and sometimes may also show flu-like symptoms. Gastrointestinal discomfort may also occur in individual cases. But the toxic and side effects can be greatly reduced if the drug is applied locally.
Strontium (Sr) is an important component of bones and has a chemical structure similar to that of calcium. The normal function of bones can be maintained if a certain proportion of strontium ions are kept in the bones. Strontium is one of the essential elements in human bones. β-Catenin is an important factor in wnt pathways. Strontium can promote the growth of osteoblasts and inhibit the activity of osteoclasts by regulating the wnt pathways. In addition, strontium salts can increase the activity of alkaline phosphatase (ALP) and synthesis of bone collagen. It is also recognized in animal experiments that strontium salts in the body can reduce bone resorption while increasing bone formation and promoting the increase of bone mass and bone strength. Moreover, the strontium salts can improve the microstructure of the trabecular bone without affecting the stability of minerals in the internal environment. Therefore, applying strontium salts to a local fracture site can not only increase the concentration of a strontium salt drug to promote the healing of the fracture site, but also reduce the systemic toxic and side effects. Collagen is a protein with the highest content in mammals, has special mechanical properties and biological characteristics, and serves the function of supporting organs and protecting the body. With the improvement of preparation processes and the development of modification technology, collagen has become a widely used biological material with an excellent performance, which can be applied to burn dressing, wound filling, hemostasis in vivo, and tissue engineered repair.